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Introgression

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plant-introductions-evolution-hybrid-speciation-and-gene-transfer-18-728nature09103-f3.2Is there a difference between admixture and introgression? I think there is. Or have always assumed there is. But of late I’m wondering if a distinction is widely accepted, and what sort of distinctions people make. That is, in some cases it seems clear that admixture and introgression are used interchangeably as meaning the same thing. I’ve seen this in scientific papers, and often just do a mental substitution. But in other cases I’m wondering if people are using the terms in a different sense than I am. Probably the latter is more worrisome.

The figure to the left was generated by Admixture, a software package which takes population genetics assumptions (models) and data, and shows you the best fit of the data to a particular model. In this case the bar plot shows you the admixture of a given individual when you posit them to be a combination of K ancestral populations. The individuals are clustered by population, so you see population-wide profiles. The details of the model, and whether the model accurately captures reality (i.e., were there actually K populations at any time in the past?), is less important for this post than the fact that Admixture is reflecting admixture on a genome-wide scale between two or more populations. The input data are represented by hundreds of thousands of single nucleotide polymorphisms distributed across the whole genome. The question of interest is whether a population can be represented as a pulse mixing even between two hypothetical groups, which were at some point phylogenetically distinct.

Introgression in contrast focuses on the question of genetic variants which are penetrating one population from another, and becoming common in the target population. A classical method of generating introgression in plant genetics was to engage in extensive backcrosses of mixed lineages with a trait of interest against a parental population. If one continued to select for a particular trait among the progeny one could introgress the trait and allele in a daughter population which was almost identical to one of the parent populations on a genome-wide scale, but identical to the other at one gene of interest. The practical reason for this is obvious. Imagine you have a variety of cold adapted rice which is susceptible to a particular type of fungal infection. Then, you have a heat adapted rice which is resistant to the fungal infection. All you want is fungal infection resistance, maintaining all the other characteristics that keep the cold adapted rice optimal for its climate. So you cross the two, and continue to cross progeny against cold adapted rice while selecting for the resistance phenotype. Eventually you’ll get the allele you want introgressed while maintaining the genetic background you want. In contrast, if you just allowed for admixture between the two lineages, you might get a population which was in between on a whole host of phenotypes which make them suboptimal for any climatic regime.

An example from human population genomics can be found in the paper Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. What occurred here is that a very common variant in Tibetans implicated altitude tolerance and adaptation seems to be phylogenetically closer to those you find in the Denisovan hominins than in other human populations. This, despite the fact that Denisovan ancestry is nearly nonexistent in Tibetans (the latest work suggests admixture in East and Southeast Asia on the order of 0.1 to 0.5%, with the highest fractions being among certain Southeast Asian and South Asian groups).

nature13408-f3 The network plot to the right illustrates the issue. On a genome-wide admixture plot Tibetans look like any East Asian population. They seem to be a mix of farmers related to the Han to the east and indigenous groups long resident at these high altitudes. But on the region around EPAS1 their genetic variation matches not modern humans, but the Denisovan hominin, which diverged ~500,000 years ago from the population gave rise to 90 to 99% of the ancestry of our own lineage.

So what happened? We know that there were low levels of hybridization between very diverged human lineages in the past. Because of genetic incompabilities it seems that in fact there was some selection against distinctive alleles from archaic lineages in our own genome. That is, the percentage of Neanderthal ancestry on the genomic level is probably lower than you’d get from doing a genealogical analysis of all lines of ancestry back to 100,000 years ago, because there has been selection against Neanderthal variants in the dominant human genetic background. But not in 51r8Ph-vcaL._SY344_BO1,204,203,200_ all cases. In a minority of instances the Neanderthal and Denisovan variants were not less fit, nor were they neutral, but rather, they were favored!

So, imagine a scenario where in the initial generation admixture between a large human population and a small Neanderthal population leads to admixture on the order of ~5% in the descendants. Over the generations due to selection against Neanderthal alleles the genomic ancestry from this group converges upon ~2.5%. But, on a subset of loci the Neanderthal alleles will have increased in frequency, and in some cases introgressed to high levels. This could be due to randomness; in a genome with billions of base pairs and tens of millions of nucleotide polymorphisms some alleles will drift up to higher frequencies randomly. But it is in the set of high frequency alleles from Neanderthals that you might find variants that have become common due to adaptive introgression. See this paper in AJHG, Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors. Immunological variation is always an excellent candidate because genetic diversity at these loci are highly favored, and long resident populations often have local adaptations.

Because my focus is generally in microevolutionary process, the sort of thing population geneticists are interested in, I’ve really not been talking about species-level dynamics (though the hominins are arguably distinct species). Much of the work on admixture and introgression is done by biologists focused on inter-specific differences, but the general framework holds I believe (in fact, questions of admixture and introgression and more clear and distinct across diverged lineages). In plants in particular hybridization and introgression are common in wild and domestic lineages.

I’m not putting this post up as definitive. When I read papers where there is talk about “introgression of ancestry” it is clear that today people are merging and bleeding the definitions. I actually checked for definitions of introgression and admixture in . Principles of Population Genetics and Elements of Evolutionary Genetics. There wasn’t anything, because debate on this issue isn’t/wasn’t very live in these fields. At this point I’m really curious what other biologists think. I still find the distinction important, and more critically, useful. If one doesn’t, I’d like to hear opinions. If one has different definitions, I’d like to hear opinions.

 
• Category: Science • Tags: Adaptation, Genetics, Introgression 
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Screenshot - 12102015 - 03:55:03 PM

Screenshot - 12102015 - 04:26:46 PM The human genome is littered with many genes from diverged lineages. That is, any given human has segments from lineages which are deeply diverged from the dominant demographic element in our ancestry, which diverged from an African population which flourished on ~200,000 years ago, and among non-Africans a population derived from Northeast Africa ~50,000 years ago. The Neanderthal ancestry of non-Africans, which is in the range of ~2 percent, diverged from the rest of the genome on the order of ~500,000 years ago from the main stem of our heritage. A similar time span divides us from the Denisovan ancestry in Oceanians, and to a lesser extent island Southeast Asians, and even less among East and South Asians. Due to the lack of ancient genomes such definitive inferences are more difficult to make for African populations, but there are suggestive clues that diverged lineages also contributed to the Khoe-San and Pygmy, and therefore other African, peoples.

Though the initial Neanderthal admixture results tended to focus on their implications for ancestry, and not function, a recent spate of work has suggested that archaic admixture in modern lineages may have been adaptive. But at some point one needs to go beyond genome-wide assessments, and look at specific genes. In that vein, a preprint out of Rasmus Nielsen’s group, Archaic adaptive introgression in TBX15/WARS2. This related to their paper about adaptation of Greenland Inuit to their environment. What they report here is that Greenlanders, and Eurasians more broadly as well, exhibit evidence of carrying an introgressed haplotype which derives from Denisovans or a Denisovan-related population.* The map above shows distributions of an allele which is strongly associated with the introgressed haplotype. You can see that it is absent in Sub-Saharan Africa, fixed in Greenland, present in high frequencies in the New World (near fixation in Amerindians), at moderate frequencies in East Asia, and lower frequencies elsewhere in Eurasia. The haplotype harbors two genes, TBX15 and WARS2. What do these genes do? Lots of things:

The TBX15/WARS2 region is highly pleiotropic: it has been found to be associated with a variety of traits. These include the differentiation of adipose tissue5, body fat distribution…facial morphology…stature…ear morphology…hair pigmentation…and skeletal development…Interestingly, for several of body fat distribution studies, the introgressed SNPs have significant genome-wide associations. The Denisovan alleles tend to increase waist circumference and waist-hip ratio, after correcting for BMI.

They went to great lengths to ascertain whether this was an introgressed haplotype, and where it came from in relation to the genomes we have on hand (Neanderthals, modern humans, and Denisovans). Broadly they are convincing that it is introgressed, and not deep structure from Africa. And, they make a good case that the population from which this haplotype derived is closer to Denisovans than to Neanderthals. The summary is really in the haplotype network above. To the bottom right you see a cluster of common human haplotypes. Then you see the Neanderthal haplotype, and then further along the Denisovan haplotype. Finally, you see a cluster of introgressed haplotypes. First, remember it’s not established that the donor population was Denisovan. Second, there have been derived mutations since the allele moved between populations.

The functional reason why this swept to fixation in Greenlanders seems obvious. It’s related to the nature of fat deposition, and GWAS correlate it with effects on BMI and body shape, and, it is jointly in high frequency in Amerindians and the populations of the Arctic. In all likelihood the sieve was in Beringia, where climatic conditions were extreme, and all sorts of adaptations were necessitated. And the authors state that plainly. In relation to mechanism there are suggestions that there regulatory and epigenetic dynamics at play. The expression differences seem clear, in terms of how the Denisovan variant effects the magnitude of the genetic consequence. But the epigenetic aspect is very confused to me. Part of it seems to be that the authors themselves are trying to make sense of the results (jump to “DMR”), but I wish they would at least expand, because there is some lack of clarity as to the details (I had a friend whose research is in epigenetics read that section and they found it a bit unclear, so they didn’t want to evaluate whether it made sense, so I felt better as to my confusion).

With all that put out there, let’s get to the crux of the issue that we can agree on. Using simulations the authors did establish that this is unlikely to have increased in frequency in all these populations simply due to drift. That is, chance. The alternative then is that selection is increasing the frequency of this haplotype, and assorted functional alleles. In the case of Amerindians you see see that it is close to fixation. There is a recessive aspect to the nature of methylation patterns, which are associated with gene expression, so that may give us a clue why this variant is fixed in Greenland, and nearly so in unadmixed Amerindians. If the expression of a favored trait is recessive, then it makes sense to make the final step from ~90% (where nearly 20% of the population would have a disfavored morph) to ~99% (where only ~2% would).

But what’s going on in Old World populations? To my knowledge there is no evidence of Denisovan admixture in western Eurasian populations, but you can find these “Denisovan” alleles in them. The simplest explanation is that the haplotype is derived from another archaic population, within the same clade as Denisovans with Neanderthals as an outgroup, which was resident further west. In fact, look at the structure the introgressed haplotypes. The Amerindians have the most diverged branch, while the western and southern Eurasian groups are represented within the haplotype closest to Denisovans. To me this is suggestive of an early admixture event closer to the point-of-departure from Africa. As modern humans moved east the serial bottleneck effect occurred with this introgressed haplotype.

A second possibility is that this allele may be from Denisovans, and that it is so favored that even if small levels of eastern Eurasian admixture don’t manifest themselves in total genome-wide admixture estimates a few copies were sufficient for this to become common outside that zone. This gets to the title of the post: one can posit a multi-regional system of selected variants sweeping across interconnected demes, which transcend the fact that migration between the demes is too low to make significant contributions to total genome content. This may explain the presence of East Asian EDAR in the Motala samples, for example.

Finally, I think one has to consider the high probability that the target of selection on this locus has varied over time and space. The introgression of this archaic allele into non-Africans was an ancient event, but it does not seem to have fixed into any populations outside of the Beringian Diaspora. Why? It may be that there are balancing effects going on, perhaps frequency dependence, or, in even over-dominance (I tend to discount the last in most cases, but the fractions in East Asia are so close to 50%). Along the East Asian littoral the frequency is in an intermediate range, while in western and southern Eurasia they’re present at lower frequencies, though lower in South Asia than in some of the European groups. This is intriguing because when it comes to alleles which are not subject to selection South Asian share more ancestry with East Eursaians, and you generally see a pattern where they occupy a position in between (e.g., this is the case when it comes to Neanderthal admixture, with East Asians having the most, and Europeans the least, with South Asians between).

There’s a lot that’s going to be researched and published between now and 2025. These authors have established that they found an introgressed variant, but it’s too widely distributed to have the neat solution that EPAS1 in Tibetans has.

* My father and brother carry one copy of the introgressed haplotype.

 
• Category: Science • Tags: Adaptation, Genomics, Introgression 
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The class human or H. sapiens refers to a set of individuals. On the grand scale it’s really not all that clear and distinct. When do “archaic” humans become “modern” humans? Taking into account human variation, what is a “human universal”? A set of organisms are given a name which denotes the reality that they may share common ancestry, and interact behaviorally, and are potential mates. But many of these phenomenon are fuzzy on the margins. Many of the same issues which emerge in the “species concept” debates are rather general up and down the scales of natural complexity. A similar problem crops up when we conflate the history of genes with the history of populations. Such a conflation has value and utility to a first approximation. The story of mitochondrial Eve was actually the history of one particular locus, the mitochondrial genome. But it did tell us quite a bit about the history of the human species, even if in hindsight it looks as if some scientists overinterpreted those findings. One of the major issues I’ve noticed over the past year, with the heightened likelihood of archaic admixture in the modern human genome, is that people regularly get confused by the difference between total genome ancestry, and the evolutionary history of one particular gene.


Consider the possibility that a substantial proportion of the genetic variants at the dystrophin locus amongst Eurasicans (non-Africans) derive from Neanderthals. As I have observed one of my siblings carries only the Neanderthal variant (males have only one copy as this gene is on the X chromosome). Does this mean he is 100% Neanderthal? Obviously not. The patterns at one gene tell you the history of that one gene. Since the patterns across genes are correlated because of shared evolutionary history (ergo, the existence of geographical racial clusters) one gene can tell you more than just its own history because you are aware of the correlations. But you can’t take this too far. My sibling is less than 5% Neanderthal across his whole genome. He just happens to be “100% Neanderthal” at that gene. There isn’t a great contradiction here. His genome is not a Platonic ideal or a pure category of human vs. non-human.

I bring this up because a few months ago I relayed the findings at a conference as to the evidence of lots of introgression into the human genome from archaic hominins on immune related loci. The paper reporting those findings is now out in Science, The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans:

Whole-genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic HLA class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.

Introgression implies more than just ancestry. These results indicate that Denisovan ancestry at particular immunologically relevant loci is rather high amongst East Asian groups which have no discernible Denisovan ancestry across the total genome. Presumably that’s an artifact of the limits of statistical power in detecting very low levels of admixture. But out of tens of thousand of genes it is not unimaginable that there are some few gene copies from exotic sources which turn out to be adaptive, and so favored over “native” alleles (cultural analogs come to mind; the Roman language remains, but the Roman religion has been replaced by a Jewish derived sect). The paper has little new beyond the conference talk. Note this result:

From the combined frequencies of these six alleles, we estimate the putative archaic HLA-A ancestry to be >50% in Europe, >70% in Asia, and >95% in parts of PNG (Fig. 4, C and D). These estimates for HLA class I are much higher than the genome-wide estimates of introgression….

More precisely, the introgression estimates are around an order of magnitude greater than admixture. Intriguingly the authors note that though most Africans exhibit some evidence of introgression from Eurasian populations, Khoisan and Pygmies do not. This seems to point to the possibility that the generic class “African” may hide a lot of interesting population structure and history. It is clear that peoples from the Horn of Africa seem to have been recently influenced by Eurasian groups, but it may be that West and East Africans more generally have been touched by deep-time back-migrations. Though I’ve been skeptical of attempts to portray Khoisan and Pygmies as “ur-humans,” these results suggest that that characterization may be closer to the mark than I had argued earlier.

(Republished from Discover/GNXP by permission of author or representative)
 
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Image credit:ICHTO

Recently something popped up into my Google news feed in regards to “Neanderthal-human mating.” If you are a regular reader you know that I’m wild for this particular combination of the “wild thing.” But a quick perusal of the press release told me that this was a paper I had already reviewed when it was published online in January. I even used the results in the paper to confirm Neanderthal admixture in my own family (we’ve all been genotyped). One of my siblings is in fact a hemizygote for the Neanderthal alleles on the locus in question! I guess it shows the power of press releases upon the media. I would offer up the explanation that this just shows that the more respectable press doesn’t want to touch papers which aren’t in print, but that’s not a good explanation when they are willing to hype up stuff which is presented at conferences at even an earlier stage.

A second aspect I noted is that except for Ron Bailey at Reason all the articles which use a color headshot use a brunette reconstruction, like the one here which is from the Smithsonian. But the most recent research (dating to 2007) seems to suggest that the Neanderthals may have been highly depigmented. This shouldn’t be too surprising when one considers that they were resident in northern climes for hundreds of thousands of years.

But there are some new tidbits, from researchers in the field of study:

“There is little doubt that this haplotype is present because of mating with our ancestors and Neanderthals,” said Nick Patterson of the Broad Institute of MIT and Harvard University. Patterson did not participate in the latest research. He added, “This is a very nice result, and further analysis may help determine more details.”

David Reich, a Harvard Medical School geneticist, added, “Dr. Labuda and his colleagues were the first to identify a genetic variation in non-Africans that was likely to have come from an archaic population. This was done entirely without the Neanderthal genome sequence, but in light of the Neanderthal sequence, it is now clear that they were absolutely right!”

The modern human/Neanderthal combo likely benefitted our species, enabling it to survive in harsh, cold regions that Neanderthals previously had adapted to.

“Variability is very important for long-term survival of a species,” Labuda concluded. “Every addition to the genome can be enriching.”

Since Nick comments here on occasion I probably should have asked him what he thought of these results back in January, but it goes to show that I’m not thinking like a journalist. Yet.

(Republished from Discover/GNXP by permission of author or representative)
 
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Update: John Hawks’ lab is working in the same area, and he disagrees with the specific results presented here. Always reminds you to be careful about sexy results presented at conference! (someone should do a study!)

So claimed Peter Parham at a Royal Society meeting last week, Human evolution, migration and history revealed by genetics, immunity and infection. You can actually listen to the talk by pulling down the mp3 file. To get the part about human evolution and introgression, jump to 24 minutes in.

Here is the general sketch: It looks like ~50 percent of the HLA Class I alleles in Europeans derive from Neandertals, ~70-80 percent of HLA Class I alleles in East Asians derive from Denisovans, and that and ~90-95 percent of HLA Class I alleles in Papuans derive from Denisovans. If you recall, ~2.5% of the total genome content of non-Africans seems to be Neandertal, while ~5% of the total genome content of Papuans seems to be Denisovan. The total genome content proportions are rough estimates, there may be some wiggle room in there. But you can see that the HLA allele admixture estimates from these ancient Eurasian lineages is greater by an order of magnitude. Why?


Parham is at pains to point out that there is a major distinction in the nature of the genealogies of alleles which have generally been buffeted by neutral dynamics, and those which have been subject to selection. The HLA region is among the most polymorphic in the human genome, and that is due to the fact that balancing selection maintains diversity (likely a great deal of this through negative frequency dependence over the long term). Presumably this is the target of selection when one conceives of the Red Queen’s Hypothesis in terms of pathogen-host immune system coevolution.

In the presentation it is clear that something seemed off in some of the HLA haplotypes which these researchers had analyzed. They “looked” as if they were introgressed. There has been evidence of this before on other genes. But, with the draft sequences of ancient Neandertals and the Denisovan, scholars could check to see if inferences of admixture between archaic and neo-African lineages were borne out by matching them against the actual sequenced ancient DNA. In some cases they did. In others instances the inferences were wrong (or, the archaic introgression was from a lineage which hasn’t been sequenced yet). In this case Parham reports that his researchers found that the alleles found at high frequency in eastern Eurasia and Oceania seem to derive from the same lineage as that of the Denisovan. Intriguingly, he also adds that the Europeans are about ~50 percent admixed at the HLA Class I locus. If I heard Parham correctly, there are two major points in relation to human evolutionary history:

- East Asians have the Denisovan allele, when they don’t have Denisovan ancestry

- They don’t have the Neandertal alleles, when they do have Neandertal ancestry

- The Papuans are nearly fixed for the Denisovan allele, and lack the Neandertal one

This is why the term “introgression” is key. We’re not talking simple admixture. Rather, admixture followed by selection, whether negative selection which purges introduced alleles, or positive selection which increases the allele’s frequency. We already saw a recent possible case of introgression with a dystrophin allele. This is much more exciting, as the HLA alleles have clear functional relevance, and are known to be targets of natural selection. If adaptation occurs via introgression, this would be one of the key candidate regions a priori. Additionally, the deviation from expectation as inferred by admixture estimates is so great that you have to wonder if selection is responsible for the difference at such a functionally relevant locus. In the East Asian case if these results hold (and I hear Parhman correctly that East Asians carry the Denisovan variant) you see a case where admixture was at such a low level that it’s not detectable, but natural selection preserved a signature of the admixture by amplifying the frequency of an introgressed allele.

In the summation of his presentation Parhman makes a lot of good points about how useful the variation of the Neandertals and Denisovans probably was for the neo-Africans. First, if they went through a bottleneck they may have lacked a large complement of HLA alleles. Because of the need for diversity at this locus to combat pathogens admixture may have been like an injection of mutations which were already preselected for a high degree of utility. Secondarily, Eurasian hominins were probably well adapted to local Eurasian pathogens. The fast that East Asians have much more detectable Neandertal ancestry (~2.5%) than Denisovan (~0.0%), but the Denisovan HLA Class I allele is much more prominent in these populations, indicates that Neandertal and Deninsovan variants were adaptive for different pathogens endemic to their regions of Eurasia!

Finally, a special shout out to Greg Cochran and John Hawks. They’ve been talking to me about introgression as a concept relevant to human evolution since 2005, so a lot of these findings are pretty unsurprising.

(Republished from Discover/GNXP by permission of author or representative)
 
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After 2010′s world-shaking revolutions in our understanding of modern human origins, the admixture of Eurasian hominins with neo-Africans, I assumed there was going to be a revisionist look at results which seemed to point to mixing between different human lineages over the past decade. Dienekes links to a case in point, a new paper in Molecular Biology and Evolution, An X-linked haplotype of Neandertal origin is present among all non-African populations. The authors revisit a genetic locus where there have been earlier suggestions of hominin admixture dating back 15 years. In particular, they focus on an intronic segment spanning exon 44 of the dystrophin gene, termed dys44. Of the haplotypes in this they suggested one, B006, introgressed from a different genetic background than that of neo-Africans. The map of B006 shows the distribution of the putative “archaic” haplotype from a previous paper cited in the current one from 2003. As you can see there’s a pattern of non-African preponderance of this haplotype. So what’s dystrophin‘s deal? From Wikipedia:

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex. Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere.

Dystrophin is the longest gene known on DNA level, covering 2.4 megabases (0.08% of the human genome) at locus Xp21. However, it does not encode the longest protein known in humans. The primary transcript measures about 2,400 kilobases and takes 16 hours to transcribe; the mature mRNA measures 14.0 kilobases….

Dystrophin deficiency has been definitively established as one of the root causes of the general class of myopathies collectively referred to as muscular dystrophy. The large cytosolic protein was first identified in 1987 by Louis M. Kunkel…after the 1986 discovery of the mutated gene that causes Duchenne muscular dystrophy (DMD) ….

OK, so we’ve established that this is not an obscure gene. Here’s the abstract of the new paper:

Recent work on the Neandertal genome has raised the possibility of admixture between Neandertals and the expanding population of H. sapiens who left Africa between 80 Kya and 50 Kya to colonize the rest of the world. Here we provide evidence of a notable presence (9% overall) of a Neandertal-derived X chromosome segment among all contemporary human populations outside Africa. Our analysis of 6092 X-chromosomes from all inhabited continents supports earlier contentions that a mosaic of lineages of different time depths and different geographic provenance could have contributed to the genetic constitution of modern humans. It indicates a very early admixture between expanding African migrants and Neandertals prior to or very early on the route of the out-of-Africa expansion that led to the successful colonization of the planet.

The authors do consider the possibility that the B006 haplotype is derived from a common haplotype spanning Eurasian hominins and northeast Africans. They reject this on the grounds that the only African populations where such sharing with Eurasians occurs occurs are known to have been subject to recent back-migration (this presumably includes the Maasai). Additionally, they assert that “oldest lineages tend to be found in South rather than North-Eastern Africa.” I’m not totally sure about the context of this assertion. Oldest lineages overall? Or for this particular locus?

In any case, here’s a table from the 2003 paper:

The peculiarity of B006 is its restriction to non-Africans, and its variance. Remember that the null hypothesis presumes and “Out of Africa,” where non-African distinctiveness should be relatively shallow. The current paper illustrates the model for how the B006 haplotype slipped into the non-African genetic background. Interestingly the authors note the presence of B006 in “a remote community of isolated indigenous Australians living in Central Australia.” Naturally the big difference between now and 2003 is the ability to compare with the Neandertal draft reference genome. They note that “In the Neandertal sequence, no information is available for 28 of these sites, 36 sites represent ancestral alleles and 13 derived alleles. Importantly, three of the derived alleles (rs17243319, rs1456729 and rs11796299 in Table S2) are absent from the African chromosomes, as in the case of the derived G of rs11795471 from within B006. Moreover, all derived alleles shared with Neandertals occur at high frequencies (0.75 and more) on a background of the extended B006 haplotype (Figure 3 and Table S2) as expected in a segment of recent Neandertal origin.”

Overall this paper illustrates two trends. First, the general one whereby research groups are going to revisit loci which exhibit signatures of admixture with Neandertals and other assorted Eurasian hominins. Prior to 2010 these results were peculiarities, published, but generally not integrated into a bigger theoretical framework (by this, I mean the scientific community did not pay much attention to the authors’ attempts to integrate their research into a counter-narrative to “Out of Africa”). Second, there will be the specific focus on particular genes with an interest in ascertaining functional significance, and possible adaptation. This is hinted at in the last sentence of the discussion: “Considering such early encounter of H.sapiens with Neandertals, a question may be raised: was this encounter coincidental and without important evolutionary consequences or…did it facilitate adaptations to novel environmental conditions that actually contributed to the successful expansion of human migrants from Africa to other continents?” Indeed.

Citation: Vania Yotova, Jean-Francois Lefebvre, Claudia Moreau, Elias Gbeha, Kristine Hovhannesyan, Stephane Bourgeois, Sandra Bédarida, Luisa Azevedo, Antonio Amorim, Tamara Sarkisian, Patrice Avogbe, Nicodeme Chabi, Mamoudou Hama Dicko, Emile Sabiba Kou’ Santa Amouzou, Ambaliou Sanni, June Roberts-Thomson, Barry Boettcher, Rodney J. Scott, & Damian Labuda (2011). An X-linked haplotype of Neandertal origin is present among all non-African populations Mol Biol Evol : 10.1093/molbev/msr024

(Republished from Discover/GNXP by permission of author or representative)
 
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480px-Olivia_MunnOne of the major issues which has loomed at the heart of biology since The Origin of Species is why species exist, as well as how species come about. Why isn’t there a perfect replicator which performs all the conversion of energy and matter into biomass on this planet? If there is a God the tree of life almost seems to be a testament to his riotous aesthetic sense, with numerous branches which lead to convergences, and a inordinate fascination with variants on the basic morph of beetles. From the outside the outcomes of evolutionary biology look a patent mess, a sprawling expanse of experiments and misfires.

A similar issue has vexed biologists in relation to sex. Why is it that the vast majority of complex organisms take upon themselves the costs of sex? The existence of a non-offspring bearing form within a species reduces the potential natural increase by a factor of two before the game has even begun. Not only that, but the existence of two sexes who must seek each other out expends crucial energy in a Malthusian world (selfing hermaphrodites obviously don’t have this problem, but for highly complex organisms they aren’t so common). Why bother? (I mean in an ultimate, not proximate, sense)

It seems likely that part of the answer to both these questions on the grande scale is that the perfect is the enemy of long term survival. Sexual reproduction confers upon a lineage a genetic variability which may reduce fitness by shifting populations away from the adaptive peak in the short term, but the fitness landscape itself is a constant bubbling flux, and perfectly engineered asexual lineages may all too often fall off the cliff of what was once their mountain top. The only inevitability seems to be that the times change. Similarly, the natural history of life on earth tells us that all greatness comes to an end, and extinction is the lot of life. The universe is an unpredictable place and the mighty invariably fall, as the branches of life’s tree are always pruned by the gardeners red in tooth and claw.

ResearchBlogging.org But it is one thing to describe reality in broad verbal brushes. How about a more rigorous empirical and theoretical understanding of how organisms and the genetic material through which they gain immortality play out in the universe? A new paper which uses plant models explores the costs and benefits of admixture between lineages, and how those two dynamics operate in a heterogeneous and homogeneous world. Population admixture, biological invasions and the balance between local adaptation and inbreeding depression:

When previously isolated populations meet and mix, the resulting admixed population can benefit from several genetic advantages, including increased genetic variation, the creation of novel genotypes and the masking of deleterious mutations. These admixture benefits are thought to play an important role in biological invasions. In contrast, populations in their native range often remain differentiated and frequently suffer from inbreeding depression owing to isolation. While the advantages of admixture are evident for introduced populations that experienced recent bottlenecks or that face novel selection pressures, it is less obvious why native range populations do not similarly benefit from admixture. Here we argue that a temporary loss of local adaptation in recent invaders fundamentally alters the fitness consequences of admixture. In native populations, selection against dilution of the locally adapted gene pool inhibits unconstrained admixture and reinforces population isolation, with some level of inbreeding depression as an expected consequence. We show that admixture is selected against despite significant inbreeding depression because the benefits of local adaptation are greater than the cost of inbreeding. In contrast, introduced populations that have not yet established a pattern of local adaptation can freely reap the benefits of admixture. There can be strong selection for admixture because it instantly lifts the inbreeding depression that had built up in isolated parental populations. Recent work in Silene suggests that reduced inbreeding depression associated with post-introduction admixture may contribute to enhanced fitness of invasive populations. We hypothesize that in locally adapted populations, the benefits of local adaptation are balanced against an inbreeding cost that could develop in part owing to the isolating effect of local adaptation itself. The inbreeding cost can be revealed in admixing populations during recent invasions.

First, plants are good models to explore evolutionary genetics. They’re not as constrained as say mammals, or the typical tetrapod, when it comes to barriers to gene flow between distinct taxa. Hybridization is common, and plants can also self-fertilize as well as cross-fertilize, allowing researchers to push the genetic pool in different directions (“selfing” obviously reduces the effective population and is an extreme form of inbreeding, so it’s a good way to purge genetic variation really quickly). In a perfect abstract world of evolution one might imagine Richard Dawkins’ vehicles and replicators as fluid entities which float along a turbid sea of evolutionary genetic parameters, drift, migration, mutation and selection. But reality is constrained to DNA substrate, which have their own parameters such as recombination, modulators such as epigenetics, and numerous ways to express variation through gene regulation. It’s complicated, and stripping the issues down to their pith is easier said that done.

But the broader dynamics here being examined is the generalist-specialist trade-off, which I think is relevant to the two issues I introduced earlier in this post. Specialists are optimized for their own position in the adaptive landscape, but have difficulties when it is perturbed. Generalists always less than maximum fitness in all landscapes, but higher average fitness across them because they can adapt to changes. Specialization is local adaptation of particular lineages, while in the generalist case you can have invasive species in novel environments. They’re obviously facing an adaptive landscape which is at some remove from what any of the introduced genotypes were “optimized” for, so hybridization produces something new for something new.

In the first figure of the paper you see F3 wild barley descended from two parental lineages, ME and AQ. The left panels show seed output as a function of heterozygosity, and the right panels as a function of ME genome content. Remember that in subsequent generations the descendants of hybrids will vary quite a big in genetics and phenotype as the original alleles re-segregate.

F1.large

The takeaway is that in novel environments genetic variation seems to result in increased fitness. Why? One concept which one has to introduce is heterosis, whereby crosses between homogeneous lineages produce more fitness offspring. One reason this may be is that there is overdominance, where heterozygotes have greater fitness than the homogyzotes. This is the case with sickle-cell malaria disease. Another reason may be that in the original parental lineages there was a higher fraction of alleles which were deleterious in homozygote genotypes. In plain English, inbreeding resulted in genetic drift which cranked up the proportion of alleles implicated in recessively express negative phenotypes. The authors argue though that in the context local adaptation is strong enough to be a barrier against too much gene flow between the parental wild barely lineages, so the deleterious alleles are less likely to be masked. Only in a novel environment when that benefit was removed from the equation could the negative consequences of inbreeding come to the fore in the total calculus.

Figure 2 shows the results of experiments which examine the fitness of white campion, a European species which has been introduced in North America. In the left panel are crosses between native European lineages, with distance between parental lineages on the x-axis. In the right panel you have the same experiment, but with North American variants, which are products of introductions from various regions of Europe. The plants were grown in a “common garden,” to show how all the genotypes performed when environment was controlled.

F2.large

As you can see moderate levels of hybridization entailed a benefit in the European variants, but not the North American variants. Hybridization between variants which were too distant did produce outbreeding depression in the European case, suggesting perhaps that disruption of co-adapted gene complexes resulted in a greater fitness cost than the masking of deleterious alleles due to inbreeding. One can make the inference from these data that the introduced white campion lineages are already hybridized, the barriers to crossing being removed by a disruption of the adaptive landscapes which each native lineages was optimized for.

Here are the authors from the discussion talking about invasions of exotic species:

Provided that multiple introductions from different source populations have occurred, the benefits of admixture become freely available to introduced populations that do not yet show a pattern of local adaptation. Because the benefits are potentially large, admixture may play an important role during early invasions. Native populations often show evidence of inbreeding depression…and one instant reward of admixture in the introduced range is the release of this genetic burden. Such heterosis effects can contribute significantly to the establishment and early success of invasive species…When tested together in a common garden experiment, invaders can show enhanced fitness-related traits compared with populations from their native range…If there is evidence of admixture, the effects of heterosis might be a default explanation for such observations, perhaps providing a null expectation against which other explanations (such as trait evolution) need to be tested.

What have plants to do with life as a whole? I assume much. Plants differ in the details, but compared to other complex multicellular organisms in regards to evolutionary genetics they’re quite liberated. By this, I mean that their modes of reproduction and promiscuity in hybridization make them more of an ideal “frictionless” test case of evolutionary biology and the power of the classical parameters. Perhaps given enough time natural selection would produce the ideal replicator to rule them all, to drive all others to extinction. But that day is not this day. And that day may never come because the universe is far too protean and erratic. Life is varied, on the phenotypic and genotypic level, and the exogenous processes of climate and geology continue to warp and reshape the adaptive landscape. And more subtly, but just as critically, life is always in an endless race with itself, as pathogens co-evolve with their hosts, and predators figure out how to outfox their prey. Life warps its own adaptive landscapes, and the innovation of one branch may lead to extinction of others as well as the proliferation of new branches.

More prosaically and anthropocentrically what does this say about us? Humans are an expansive species, and over the past 500 years different lineages have been hybridizing promiscuously. New genotypes have arisen in altered landscapes, and our pathogens are also riding the high tide of globalization onward and upward. We are ourselves a “natural experiment.”

Image Credit: Olivia Munn by Gage Skidmore

Link hat tip: Dienekes.

Citation: Verhoeven KJ, Macel M, Wolfe LM, & Biere A (2010). Population admixture, biological invasions and the balance between local adaptation and inbreeding depression. Proceedings. Biological sciences / The Royal Society PMID: 20685700

(Republished from Discover/GNXP by permission of author or representative)
 
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Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at http://www.razib.com"